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You searched for +publisher:"IUPUI" +contributor:("Hoang, Quyen Q."). Showing records 1 – 3 of 3 total matches.

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1. Washburn, J. Alex. Exploring Dual-Targeting GroEL/ES & PtpB Inhibitors as a New Antibiotic Strategy for Tuberculosis.

Degree: 2019, IUPUI

Indiana University-Purdue University Indianapolis (IUPUI)

Current Mycobacterium tuberculosis (Mtb) treatments suffer from an increase in antibiotic resistance strains and the lack of efficacy against latent state tuberculosis, thus novel approaches targeting different mechanisms of action are needed. One strategy to target Mtb is to target protein homeostasis pathways by inhibiting molecular chaperones, in particular, GroEL/ES (HSP60/10) chaperonin systems. Mtb has two homologs of GroEL, of which GroEL1 is not essential, but is important for cytokine-dependent granuloma formation, and GroEL2 is essential for survival and the likely canonical housekeeping chaperonin. Another strategy to target Mtb is to target the protein tyrosine phosphatase B (PtpB) virulence factor that Mtb secretes into host cells to help evade immune responses. Thus, we envisioned that this analog series might also be capable of inhibiting Mtb PtpB along with GroEL. By developing compound 1 inhibitors that could act on all of GroEL1, GroEL2, and PtpB, we could have an antibiotic candidate that targets all stages of tuberculosis: actively replicating bacteria, bacteria evading host cell immune response, and granuloma formation in latent disease. In the Johnson lab, previous studies explored GroEL/ES inhibitors, with compound 1 being one of the most potent inhibitors, inhibiting both Trypanosoma brucei and Staphylococcus aureus proliferation. In the present study, we have screened previously developed compound 1 analogs, as well as a series of newly synthesized analogs that we term “half-molecules”. In this study, our results indicated two potential avenues to explore for future research. The first is a series of carboxyl-bearing compound 1 inhibitors, compounds 2m-o, 2m-m, and 2m-p, which act solely on Mtb PtpB phosphatase activity without inhibiting GroEL. The second is a series of compound 1 inhibitors (e.g. 20R and 20L) that are able to inhibit both the PtpB phosphatase and GroEL/ES chaperonin system. Thus, this exploratory study showed the possibility of pursuing such a polypharmacological antibiotic strategy against Mtb infections and with further optimization, such dual-targeting GroEL/ES and PtpB inhibitors could be effective against all stages of tuberculosis.

Advisors/Committee Members: Johnson, Steven M., Georgiadis, Millie M., Hoang, Quyen Q..

Subjects/Keywords: GroEL; PtpB; Tuberculosis; HSP60

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Washburn, J. A. (2019). Exploring Dual-Targeting GroEL/ES & PtpB Inhibitors as a New Antibiotic Strategy for Tuberculosis. (Thesis). IUPUI. Retrieved from http://hdl.handle.net/1805/19379

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Washburn, J Alex. “Exploring Dual-Targeting GroEL/ES & PtpB Inhibitors as a New Antibiotic Strategy for Tuberculosis.” 2019. Thesis, IUPUI. Accessed December 04, 2020. http://hdl.handle.net/1805/19379.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Washburn, J Alex. “Exploring Dual-Targeting GroEL/ES & PtpB Inhibitors as a New Antibiotic Strategy for Tuberculosis.” 2019. Web. 04 Dec 2020.

Vancouver:

Washburn JA. Exploring Dual-Targeting GroEL/ES & PtpB Inhibitors as a New Antibiotic Strategy for Tuberculosis. [Internet] [Thesis]. IUPUI; 2019. [cited 2020 Dec 04]. Available from: http://hdl.handle.net/1805/19379.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Washburn JA. Exploring Dual-Targeting GroEL/ES & PtpB Inhibitors as a New Antibiotic Strategy for Tuberculosis. [Thesis]. IUPUI; 2019. Available from: http://hdl.handle.net/1805/19379

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


IUPUI

2. Kunkle, Trent A. Antibiotic Discovery Targeting Bacterial GroEL/GroES Chaperonin Systems.

Degree: 2018, IUPUI

Indiana University-Purdue University Indianapolis (IUPUI)

The Centers for Disease Control (CDC) and World Health Organizations (WHO) have highlighted six species of highly drug-resistant bacteria, commonly termed the ESKAPE pathogens, that new antibacterials are urgently needed to treat). The ESKAPE pathogens account for over two-million infections and have healthcare costs upwards of $20 billion dollars annually. Over the past several decades, pharmaceutical companies have drastically reduced their research programs for developing new antibacterial agents. As well, bacteria are predisposed to rapidly generate resistance against these “me too” drugs, making this strategy a temporary stop-gap in our ability to fight these pathogens. This has left the burden to identify new antibiotics that function through fundamentally unique mechanisms of action to academia. Towards this goal, we are developing a unique antibacterial strategy that functions through targeting the bacterial GroEL chaperonin systems. GroEL is a molecular chaperone that helps fold proteins into their functional states. Being an essential protein, inhibiting GroEL activity leads to global aggregation and bacterial cell death. We previously reported a high-throughput screening effort that identified 235 GroEL inhibitors. A subsequent study with a subset of these inhibitors identified several that kill bacteria. To follow-up, we have synthesized 43 analogs of a hit-to-lead molecule, compound 1, containing systematic deletions of substituents and substructures to determine the essential parts of the scaffold for inhibiting GroEL and killing bacteria. Along with inhibiting GroEL, several compound 1 analogs exhibit >50-fold therapeutic windows between antibacterial efficacy and cytotoxicity to human liver and kidney cells in cell culture. Evaluation of two lead candidates (1 and 11) in a gain-of-resistance assay indicated that MRSA bacteria were not able to easily generate resistance to this compound class. Compound 1 also exhibited the ability to permeate through already established S. aureus biofilms and maintain its bactericidal effects, whereas vancomycin could not. Having established initial structure-activity relationships for the compound 1 substituents and substructures in this study, future efforts will focus on optimizing the antibacterial effects of lead candidates and reducing their off-target toxicity to human cells.

Advisors/Committee Members: Johnson, Steven M., Georgiadis, Millie M., Hoang, Quyen Q..

Subjects/Keywords: Antibiotics; Bacteria; Resistance; Chaperonin

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Kunkle, T. A. (2018). Antibiotic Discovery Targeting Bacterial GroEL/GroES Chaperonin Systems. (Thesis). IUPUI. Retrieved from http://hdl.handle.net/1805/17427

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Kunkle, Trent A. “Antibiotic Discovery Targeting Bacterial GroEL/GroES Chaperonin Systems.” 2018. Thesis, IUPUI. Accessed December 04, 2020. http://hdl.handle.net/1805/17427.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Kunkle, Trent A. “Antibiotic Discovery Targeting Bacterial GroEL/GroES Chaperonin Systems.” 2018. Web. 04 Dec 2020.

Vancouver:

Kunkle TA. Antibiotic Discovery Targeting Bacterial GroEL/GroES Chaperonin Systems. [Internet] [Thesis]. IUPUI; 2018. [cited 2020 Dec 04]. Available from: http://hdl.handle.net/1805/17427.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kunkle TA. Antibiotic Discovery Targeting Bacterial GroEL/GroES Chaperonin Systems. [Thesis]. IUPUI; 2018. Available from: http://hdl.handle.net/1805/17427

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


IUPUI

3. Howe, Christopher Ryan. Analogues of Nitrofuran Antibiotics are Potent GroEL/ES Pro-drug Inhibitors with Efficacy against Enterococcus Faecium, Staphylococcus Aureus, and Escherichia Coli.

Degree: 2020, IUPUI

Indiana University-Purdue University Indianapolis (IUPUI) Advisors/Committee Members: Johnson, Steven M., Hoang, Quyen Q., Meroueh, Samy O..

Subjects/Keywords: Pro-Drugs; GroEL/ES; Chaperone Proteins; Nitrofurans; Hydroxyquinolines; Nitroreductases; Inhibitors

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Howe, C. R. (2020). Analogues of Nitrofuran Antibiotics are Potent GroEL/ES Pro-drug Inhibitors with Efficacy against Enterococcus Faecium, Staphylococcus Aureus, and Escherichia Coli. (Thesis). IUPUI. Retrieved from http://hdl.handle.net/1805/22885

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Howe, Christopher Ryan. “Analogues of Nitrofuran Antibiotics are Potent GroEL/ES Pro-drug Inhibitors with Efficacy against Enterococcus Faecium, Staphylococcus Aureus, and Escherichia Coli.” 2020. Thesis, IUPUI. Accessed December 04, 2020. http://hdl.handle.net/1805/22885.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Howe, Christopher Ryan. “Analogues of Nitrofuran Antibiotics are Potent GroEL/ES Pro-drug Inhibitors with Efficacy against Enterococcus Faecium, Staphylococcus Aureus, and Escherichia Coli.” 2020. Web. 04 Dec 2020.

Vancouver:

Howe CR. Analogues of Nitrofuran Antibiotics are Potent GroEL/ES Pro-drug Inhibitors with Efficacy against Enterococcus Faecium, Staphylococcus Aureus, and Escherichia Coli. [Internet] [Thesis]. IUPUI; 2020. [cited 2020 Dec 04]. Available from: http://hdl.handle.net/1805/22885.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Howe CR. Analogues of Nitrofuran Antibiotics are Potent GroEL/ES Pro-drug Inhibitors with Efficacy against Enterococcus Faecium, Staphylococcus Aureus, and Escherichia Coli. [Thesis]. IUPUI; 2020. Available from: http://hdl.handle.net/1805/22885

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.